Jieya Shao, Ph.D.

Assistant Professor
Internal Medicine

Cancer Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-8695

  • 314-747-9310

  • 314-747-9320

  • 4515 McKinley Building, 3rd floor

  • shao.j@wustl.edu

  • www.shaolab.org

  • breast cancer, targeted therapy, protein trafficking, dynamics, gene regulation, DNA damage response, phosphorylation, ubiquitination

  • Understanding the "moonlighting" functions and therapeutic potential of novel cancer targets

Research Abstract:

Cancer is a complex disease driven by various aberrant events. Targeted therapies, though conceptually straightforward, are practically challenging due to the complex biology of many cellular targets. We are interested in unravelling the biology of novel cancer targets with the ultimate goal of improving existing therapies and developing new treatments. Currently we are focusing on two research areas in the context of breast cancer.

1) Profilin-1: an old protein with new functional twists

Profilin-1 (Pfn1) is a well-characterized actin-binding protein essential for cell proliferation, survival and migration, yet showing paradoxical antitumor and anti-metastatic effects in several types of cancer including breast. We have recently proposed a “spatial confinement” model to reconcile its opposing functions. We hypothesize that Pfn1 has poorly understood functions in the nucleus in addition to its cytoplasmic actin-remodeling activity, and it is the nuclear "moonlighting" functions that underlie Pfn1`s anticancer effects. We are currently utilizing multi-disciplinary approaches (biochemistry, cell biology, imaging, epigenetics, mouse tumor models) to investigate the nuclear functions of Pfn1 and its mode of deregulation in cancer, and explore opportunities to therapeutically target its activity.

​2) p97/VCP: a polyubiquitin-specific protein "segregase" orchestrating DNA damage response

Valosin-containing protein (VCP) is an evolutionarily conserved AAA+ ATPase involved in diverse cellular processes. Functioning as a “segregase”, VCP facilitates protein homeostasis by extracting polyubiquitinated proteins from various cellular locations or complexes for subsequent turnover. Recent studies have linked VCP to chromatin-associated protein degradation and genome stability maintenance particularly in the context of DNA damage response (DDR). However, detailed understanding of its mechanism of action, its mode of (de)regulation in cancer, and its relevance to cancer treatments is lacking, and we are currently studying all these questions.

Selected Publications:

Lei JT*, Shao J*, Zhang J*, Iglesia M*, Chan DW, Cao J, Anurag M, Singh P, He X, Kosaka Y, Matsunuma R, Crowder R, Hoog J, Phommaly C, Goncalves R, Ramalho S, Peres RMR, Punturi N, Schmidt C, Bartram A, Jou E, Devarakonda V, Holloway KR, Lai WV, Hampton O, Rogers A, Tobias E, Parikh PA, Davies SR, Li S, Ma CX, Suman VJ, Hunt KK, Watson MA, Hoadley KA, Thompson EA, Chen X, Kavuri SM, Creighton CJ, Maher CA, Perou CM, Haricharan S, Ellis MJ. (2018) Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer. Cell Rep. 24(6):1434-1444. PMID: 30089255 *These authors contributed equally to this work.

Gates LA, Gu G, Chen Y, Rohira AD, Lei JT, Hamilton RA, Yu Y, Lonard DM, Wang J, Wang SP, Edwards DG, Lavere PF, Shao J, Yi P, Jain A, Jung SY, Malovannaya A, Li S, Shao J, Roeder RG, Ellis MJ, Qin J, Fuqua SAW, O`Malley BW, Foulds CE. (2018) Proteomic profiling identifies key coactivators utilized by mutant ERα proteins as potential new therapeutic targets. Oncogene. PMID: 29748621

Wardell SE, Ellis MJ, Alley HM, Eisele K, VanArsdale T, Dann SG, Arndt KT, Primeau T, Griffin E, Shao J, Crowder RJ, Lai JP, Norris JD, McDonnell DP, Li S. (2015) Efficacy of SERD/SERM Hybrid-CDK4/6 inhibitor combinations in models of endocrine therapy resistant breast cancer. Clinical Cancer Research, 21(22):5121-30. PubMed PMID: 25991817.

Diamond MI, Cai S, Boudreau A, Carey CJ Jr, Lyle N, Pappu RV, Swamidass SJ, Bissell M, Piwnica-Worms H, Shao J. (2015) Subcellular localization and Ser-137 phosphorylation regulate tumor-suppressive activity of profilin-1. Journal of Biological Chemistry, 290(14):9075-86. PubMed PMID: 25681442; PubMed Central PMCID: PMC4423694

Li S*, Shen D*, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ. (2013) Endocrine-therapyresistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Reports, 26;4(6):1116-30. *These authors contributed equally to this work. PubMed PMID: 24055055; PubMed Central PMCID: PMC3881975

Shao J, Welch WJ, Diprospero NA, Diamond MI. (2008) Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Molecular and Cellular Biology, 28(17):5196-208. PubMed PMID: 18573880; PubMed Central PMCID: PMC2519718

Last Updated: 8/10/2018 8:14:10 AM

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